Malaria due to Plasmodium vivax is a major health burden, affecting hundreds of millions of people each year. There is increasing awareness that P. vivax causes severe and life-threatening malaria, and it is acknowledged that an effective vaccine is necessary for P. vivax malaria control and elimination. Despite the need for a P. vivax vaccine, we know relatively little about the correlates of host immunity to P. vivax. Identifying te parasite antigens that are targets of host immunity is a key step to developing an efficacious vaccine. The objective of this proposal is to identify conserved antigenic correlates of P. vivax humoral immunity and to validate their clinical relevance. To accomplish this goal, we will use a novel combination of high-throughput approaches - combining a whole-proteome screen for antigen-antibody interactions and a genome-wide scan for selection. Though both of these methods are well developed, this proposal will be the first time this combination approach has been used to study the correlates of immunity against a pathogen. The Specific Aims of this proposal are: (1) A whole-proteome scan to identify P. vivax antigens that are targeted by human antibodies, (2) A genome-wide scan for selection to identify conserved P. vivax antigens, and (3) A case-control study to validate potential antigenic correlates of host immunity against P. vivax hyperparasitemia. Through this research proposal and the carefully designed training plan, I will achieve the following fellowship goals: (1) develop technical skills in population genetics, immunology, and epidemiology? (2) develop the scientific acumen to integrate my clinical and research interests? and (3) develop the professional skills necessary for a successfu academic career.